Fungistatic preparations



Patented Nov. 11 1952 UNITED STATES FUNGISTATIC PREPARATIONS Hans Gysin, Basel ian d Ernst Hodel, Birsfelden, near Basel, Switze and, assignors to J. R. Geigy A.. G., Basel,

erland, a Swiss firm No Drawing. ApplicationMai-ch 6, 1950, Serial No. 148,012. In Switzerland March 11 1949,

This invention relates to a new fungista tie agent and provides composite fungistatic prepai rations, useful in controlling pathogenic fungi; which cause affections of the human skin. These afiections are serious human conditions Ofjdl' 'matology as well flSiDf general hygiene. {1

It .has been found that 2.9-dimethyl{l.l0 phenanthroline has an excellent fungistatic; em; cacy. When this compound is combined with an appropriate pharmaceutic vehicle, valuable composite fungistatic preparations are obtainedior treating mycotic conditions of the human skin.

2.9-dimethyl-1.IO-phenanthroline is a known. substance. It may be obtained by condensation of.o-phenylenedian lnaor of S-aminoquinaldine with one or two mols of crotonaldehyde and has "a melting point of 160 C. (see F. H. Case, J .Am.

Chem. 300., vol."70 [1948], page 3994). A 2.9-dimethyl -1 .l0rphenanthroline has proved to. beveryeilicient against: I r Trichophyton, e. g. T. interdigitale, and Epider mophyton, e. g. E..floccpsum. y y f Non-fatty arid fat containing ointmentsare suitable formsof. application to combat f ungi. on human skin, Ointments of the oil in w tei emulsion type are a particularly advantageous: form of application, as in these the active ingredient is still active in particularly large dilutions. Solutions in o f'ganic solvents which mix;w itl i water, such as'alcohol, acetone, propylene g-lyc9lj'30 glycerine (tinctures) and lotions which have ,to] be shakemar'e other suitable forms of application for the same' purpose. 0. 1-0.5% is the most -ad; vantageous concentratlon'of active ingredient these agents, butin certain cases higher or lower 33-9 concentrationsmay be used.

To increase the range'of action of 2.9-dimethylphenanthroline it canxalso .be combined-with known disinfectant bactericidal: agents such as quaternary ammonium compounds, phenols, oxy- 4 quinoline derivatives, also with acaricidal or insecticidal agents such as'crotonic acid-N-ethylo-toluidide or with-other fungicidal agents such as sulphur, salicylic acid, propionic acid and their salts, sodium benzoate, organic mercury compounds.

Some typical forms of execution of the invention are described in the following examples without, however, limiting it to the same. Parts are always given as parts by weight where not other- 2 wise stated, and temperatures are in degrees centigrade..

To test the activity The activity of'2.9-dimethyl-l.l0 phenanthro line was determined according to the diffusion method in Agar (E. J. Foley and S. W. Lee, J.

.Amer. Pharm. Assoc. 1947, 198), which was modified a little for this purpose.

Trish op): yto-n asteroides Trlchophyton rubrum Microsporum mom... Micrcsporum audizuim' Candida albica'ns... n-

Nocardia asteroidea Aclinomyces madurue meals-inc ammonia-05 oioacmo cnmcocomcamg Fat-containing ointment-of the water in oil emulsion. type 1 n Part3 Activeingredient-tenementhaunts; -0.5 Petroleum jelly 35 Wool fat 30 Parafiin oil 14.5 Water 20 The petroleum jelly, wool fat and paraflln oil are melted and the water added to form an emulsion. After coo1ing,.the active ingredient is mixed into the ointment. The active ingredient can, however, be dissolved and incorporated at another phase. This can also be done in the following examples.

EXAMPLE 2 Fat-containing ointment of the oil in water emulsion type Parts Emulsifyingmixture 15 Parafiin oil 7.5 White beeswax 5 Distilled water 72 Active ingredient 0.5

lhe emulsifying mixture (mixture of higher alcohols, their sulphonates and esters of higher fatty acids) wax and paraflin oil are melted and at 65 water of the same temperature is added to form an emulsion. The emulsion is stirred until cold and the active ingredient is then mixed '20 Th mtl1yl celluloseis thiclgened in water and on attaining the desired thickness, the active red t n elt r nef 'e s othe f k n nesub t s ch P i tragacanth, etc. can be us ed'in the place of methyl cellulose.

EXAMPLE 4 Ointment-like emulsion V 1 Parts Active ingredient 0.5 Stearic acid l 15 Triethanolaniine 1.5 Glycerine l 10 Water 73 The stearic. acid is melted, the water, glycerine and triethanolamine are heated to 70 and then added to the molten stearic acid to form an emulsion. After cooling, the active ingredient is added.

EXAMPLE 5 Lotion to be shaken Parts Active ingredientu'u 0.5 Zinc oxide; 1 15 Talc s '15 .Glycerine 30 Water 39.5

Theactive ingredient, zinc oxide-and talc are mixed-togetherand then mixed with the-glycerine and water. Titanium oxide may also be used instead of zinc oxide.

4 EXAMPLE 6 Tinctm'e Active ingredient, 0.5 part Diluted alcohol, ad. 100.0 parts by volume The active ingredient dissolves in alcohol. Also other solvents such as glycerine, isopropyl alcohol, acetone or mixtures of solvents may be used.

What we claim is:

1. A composite fungistatic preparation adapted for the treatment of mycotic conditions of the human skin comprising as its essential active fungistatic ingredient 2.9-dimethyl-1.1'0-phenanthroline uniformly distributed through an innocuous vehicle compatible with human skin and being a member selected from the group consisting of creamy vehicles, liquid vehicles comprising awateriniscible organic solvent, and pule 'verulent vehicles dispersed in a Water miscible organic solvent, said preparation being adapted to be administered to the affected tissue, said active ingredient being present in said preparation to the extent of from about 0.1 up to about 2.5%.

2. A composite fungistatic ointment adapted for the treatment of mycotic conditions of the human skin comprising as its essential active fungistatic ingredient 2.9-di'methyl-1.lll-phenan-r throline uniformly distributed through an innocuous creamy vehicle compatiblewith living human skin tissue, said preparationbeing-adapted to be smeared over the affected skin, said active ingredient being-present in said preparation to the extent of from about 0.1% up 'to about 2.5%.

3, A composite fungista'tic preparationadapted for the treatment of mycotic conditions of the human skin comprising as its essential active fungistatic ingredient 2.9-dimethyl-1.l0-phenanthroline uniformly distributed in an innocuous liquid vehicle compatible with living tissue and comprising a water miscible solvent, said prep-1 aration being adapted'to be spread over the afiected tissue, said active-ingredient being present. in said preparation to the extentof from about 0.1% up to about 2.5%.

4. A composite fungistati'cpreparation adapt-; ed for the treatment ci -prevention of mycotic conditions ofth'e humans'kin comprising as its .es-. sen'tialfactive fungistatic ingredient 2.9-dimethyl"- 1.10 phenantliroline uniformly distributed throng-n an innocuous fp'ulverulent vehicle compatible withliving skin tissue and dispersed in a water miscible organic solvent, said preparation being adapted to be spread over the afie ct'e'd' ti'ss'ule, saidactive'ingredient being present in said preparation to the extent of from 0.5%" up 'to about-2.5%

HANS GYSIN.

. ERNST HUDEL.

REFERENCES "CITE-D The following references'are of record in-the file of this patent:

V UNITEDSTATES PATENTS Name Date 2,362,614 Calva Nov. 14, 194;

about 

1. A COMPOSITE FUNGISTATIC PREPARATION ADAPTED FOR THE TREATMENT OF MYCOTIC CONDITIONS OF THE HUMAN SKIN COMPRISING AS ITS ESSENTIAL ACTIVE FUNGISTATIC INGREDIENT 2.9-DIMETHYL-1.10-PHENANTHROLINE UNIFORMLY DISTRIBUTED THROUGH AN INNOEUOUS VEHICLE COMPATIBLE WITH HUMAN SKIN AND BEING A MEMBER SELECTED FROM THE GROUP CONSISTING A CREAMY VEHICLES, LIQUID COMPRISING A WATER MISCIBLE ORGANIC SOLVENT, AND PULVERULENT VEHICLE DISPERSED IN A WATER MISCIBLE ORGANIC SOLVENT, SAID PREPARATION BEING ADAPTED TO BE ADMINISTERED TO THE AFFECTED TISSUE, SAID ACTIVE INGREDIENT BEING PRESENT IN SAID PREPARATION TO THE EXTENT OF FROM ABOUT 0.1% UP TO ABOUT 2.5%. 